Assessment of the systemic effects of beclomethasone dipropionate inhaled via Easyhaler or via Diskhaler in healthy male volunteers

Abstract.

Objective: The objective of this study was to compare the systemic effects of a moderate dose (800 µg/day) with the highest recommended dose (1600 µg/day) of beclomethasone dipropionate (BDP) inhaled via either Easyhaler or Diskhaler in 15 healthy adult male volunteers. Methods: This was an open, placebo-controlled, randomised study conducted according to a crossover design and consisting of a 1-week baseline period and five 1-week treatment periods, each separated by a 1-week washout period. Subjects received in randomised order 800 µg/day BDP via Easyhaler, 1600 µg/day BDP via Easyhaler, placebo via Easyhaler, 800 µg/day BDP via Diskhaler and 1600 µg/day BDP via Diskhaler. Subjects inhaled BDP twice daily at 0800 hours and 2000 hours. The last dose of each period was inhaled at the study site. Venous blood samples were drawn prior to and at 2-hour intervals for 20 h after the last dose. Serum cortisol area under the curve (AUC_0–20) and morning serum cortisol values were determined using radioimmunoassay. Urine for analysis of urine cortisol/creatinine ratios (UCC) was collected over a 12-h period after the last dose of each treatment period. Results: According to serum cortisol values, no systemic effects were detected with BDP 800 µg/day inhaled via Easyhaler. The mean (±SD) change in serum cortisol AUC_0–20 was +118.3±1391 nmol h/l compared with placebo. Mean (SD) changes from placebo in serum cortisol AUC_0–20 values after BDP 1600 µg/day were –546.3±1004 nmol h/l with Easyhaler and –769.3±596 nmol h/l with Diskhaler. However, there were no statistically significant differences in systemic bioactivity between the active treatments. Morning serum cortisol levels and UCC ratios were consistent with the serum cortisol AUC_0–20 data. Conclusions: In conclusion, BDP 800 µg/day inhaled via Easyhaler did not reduce serum cortisol AUC_0–20 compared with placebo. Although the decrease in hypothalamic–pituitary–adrenal (HPA) axis function after BDP 1600 µg/day was statistically significant compared with placebo, the reduction was small and similar with both devices.